The ability to maintain organs by gravity-fed oxygenated perfusion fluids was described as early as 1907 by Locke. Perfusion of oxygenated, balanced salt solutions containing sugars to meet energy requirements was shown to be superior to earlier perfusion systems where no sugars nor oxygenation was employed. Living hearts have been maintained viable for 24 hours using those early systems. Preservation of hearts for subsequent transplantation into a recipient animal was also described in literature in 1960 as was the benefit of chilling the organs to 4.degree. C. in the storage condition.
The art and science of organ transplantation has developed rapidly since 1960, due largely to improved methods of suppressing immune rejection of the transplanted organ by the transplant recipient. Presently, donor organs are collected under sterile conditions and are transported to the operating room of a designated base facility where the transplant recipient is standing by. Transportation of the organ is done using portable insulated containers kept at 4.degree. C. by blocks of ice, the organ itself being suspended in a container bathed by the balanced, chilled solution. However, perfusion of fluid through the vessels or cavities of the organ is not practiced nor is oxygenation of the solutions, although the value of such procedures is established and widely recognized. Failure to apply these preferred methods is due to the excess quantity of oxygen required to circulate oxygenated fluid through the pressure dependent perfusion pumps.
Practical use of oxygenated perfusion requires that the organ transport apparatus be self-contained, pump for a minimum of 24 hours and have compact size and low weight so that one person can carry the entire apparatus unassisted. Its size should allow ready transport in standard vehicles such as small cars, helicopters, and jet aircraft. Since fluid oxygenation and organ perfusion are not presently used, the distance between donor and recipient is severely restricted as unperfused hearts progressively deteriorate. Four hours is regarded as the upper limit that a viable organ can be transplanted with a margin of anticipated success.
The ability to transport perfused and oxygenated organs over longer distances and/or for longer times would significantly improve the successful use of donor organs because (1) organs would be in better physiological condition; (2) a larger selection of donor organs might become available; (3) time for better donor matching could influence better organ acceptability; (4) potential recipients might not have to be restricted to a base site; (5) surgical teams could have more predictable scheduling; (6) recipients of better quality organs would likely have a shorter clinical recovery and thus better well-being as well as cost saving; (7) a world-wide network of donors and recipients would be feasible.
The use of perfused, oxygenated and nutrient-balanced salt solutions at a reduced temperature enhances the viability of the transplant organ in several ways: lowering of the perfusion fluid and organ temperature lowers the metabolic activity of the organ's cells and hence reduces the demand for physiologic oxygen levels and consumption of nutrients. Reduction in cell metabolism also reduces the rate of production of by-products of metabolism such as CO.sub.2 and lactic acid, thus further reducing tissue damage and stabilizing perfusate pH and osmotic balance. Lowering of the temperature reduces the demand for oxygen and hence protects against inadequate oxygen levels that could result in ischemic tissue. In whole blood perfusate, oxygen transport is enhanced as a consequence of the hemoglobin in red blood cells serving to load, transport, and unload the oxygen in tissues of lower oxygen concentration.
Since perfusion fluids typically do not contain red blood cells, oxygen transportation is a function of the direct solubility of the gas phase (oxygen) in the perfusate solution, also being dependent upon the partial pressure of the gas phase driving gas in the liquid perfusate. Hence, satisfactory oxygen transport is achieved by exposing the perfusate to a gas phase under pressure, the pressure available being limited by the design of the oxygenating chamber and also by the limits of perfusion pressure that can be applied within the vessels of the perfused organ without causing damage. Because of the low oxygen demand of chilled tissue, the solubility of oxygen in water under low partial pressure is adequate to supply cell-tissue needs for maintenance oxygen levels.